LIBERTI: A SMART study in plastic surgery

Background/aims: Laser treatment of burns scars is considered by some providers to be standard of care. However, there is little evidence-based research as to the true benefit. A number of factors hinder evaluation of the benefit of laser treatment. These include significant heterogeneity in patient response and possible delayed effects from the laser treatment. Moreover, laser treatments are often provided sequentially using different types of equipment and settings, so there are effectively a large number of overall treatment options that need to be compared. We propose a trial capable of coping with these issues and that also attempts to take advantage of the heterogeneous response in order to estimate optimal treatment plans personalized to each individual patient. It will be the first large-scale randomized trial to compare the effectiveness of laser treatments for burns scars and, to our knowledge, the very first example of the utility of a Sequential Multiple Assignment Randomized Trial in plastic surgery. Methods: We propose using a Sequential Multiple Assignment Randomized Trial design to investigate the effect of various permutations of laser treatment on hypertrophic burn scars. We will compare and test hypotheses regarding laser treatment effects at a general population level. Simultaneously, we hope to use the data generated to discover possible beneficial personalized treatment plans, tailored to individual patient characteristics. Results: We show that the proposed trial has good power to detect laser treatment effect at the overall population level, despite comparing a large number of treatment combinations. The trial will simultaneously provide high-quality data appropriate for estimating precision-medicine treatment rules. We detail population-level comparisons of interest and corresponding sample size calculations. We provide simulations to suggest the power of the trial to detect laser effect and also the possible benefits of personalization of laser treatment to individual characteristics. Conclusion: We propose, to our knowledge, the first use of a Sequential Multiple Assignment Randomized Trial in surgery. The trial is rigorously designed so that it is reasonably straightforward to implement and powered to answer general overall questions of interest. The trial is also designed to provide data that are suitable for the estimation of beneficial precision-medicine treatment rules that depend both on individual patient characteristics and on-going real-time patient response to treatment.

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33 An Evidence Based Laser Therapy Algorithm for the Treatment of Burn Scars

Journal of Burn Care & Research ◽

10.1093/jbcr/irab032.037 ◽

2021 ◽

Vol 42 (Supplement_1) ◽

pp. S26-S27

Author(s):

Rajiv Sood

Keyword(s):

Laser Treatment ◽

Laser Therapy ◽

Co2 Laser ◽

Statistical Significance ◽

Evidence Based ◽

Baseline Measurement ◽

Burn Scar ◽

Therapy Algorithm ◽

Laser Treatments ◽

The Impact

Abstract Introduction Hypertrophic scarring after burn injury can be extremely painful, cause profound itching, and affect the way patients view themselves and how the outside world perceives them. We have utilized laser therapy as a modality for scar modulation for our patients since 2013. In 2014, we initiated and completed a prospective IRB approved study to evaluate the outcome of scars treated with fractional CO2 laser therapy (FLT) utilizing objective and subjective tools. Recently, we have completed a prospective study evaluating the use of pulse dye laser (PDL) therapy and the impact on post-burn pruritis. In reviewing the outcomes from these two studies, we have developed an evidence-based laser therapy algorithm for burn scar management. Methods The FLT study entailed a series of three CO2 laser treatments minimally 4–6 weeks apart with scar measurements and POSAS form completion performed prior to each laser treatment and four weeks after the last FLT. Scar measurements that included color, pliability, and scar thickness; and completion of the POSAS form were obtained prior to each laser therapy session and four weeks after the third laser treatment. The measurements of color, pliability, and scar thickness were measured with the Colorimeter, Cutometer, and ultrasound. The PDL study utilized the 5-D Itch scale to evaluate post-burn pruritis. A baseline measurement was obtained prior to any laser treatments. Each patient underwent two PDL sessions and a 5-D itch scale was completed four to six weeks after the second PDL session. The baseline measurement was then compared to the final 5-D itch scale measurement. Results Data from the FLT study is in Table 1 and shows that there were statistically significant improvements in the Patient and Observer POSAS scores, patient rated Itch score, scar thickness, and measured skin density. Changes to patient rated scar pain, scar color, and pliability were noted but were not of statistical significance. Data from the PDL study is in Table 2 and shows a statistically significant decrease in the treated patients’ post-burn pruritis. Conclusions In reviewing the outcomes of these two studies, we have developed an algorithm based on our studies. All of our patients undergoing laser therapy receive two PDL sessions that are four to six weeks apart followed by 3 FLT sessions. The use of both PDL and FLT decreases post-burn pruritis, decreases scar thickness, decreases pain, and increases patient satisfaction as shown in our research.

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A Sequential Multiple Assignment Randomized Trial (SMART) study of medication and CBT sequencing in the treatment of pediatric anxiety disorders

BMC Psychiatry ◽

10.1186/s12888-021-03314-y ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Bradley S. Peterson ◽

Amy E. West ◽

John R. Weisz ◽

Wendy J. Mack ◽

Michele D. Kipke ◽

...

Keyword(s):

Anxiety Disorder ◽

Anxiety Disorders ◽

Randomized Trial ◽

The Other ◽

Smart Study ◽

Main Effect ◽

Multiple Assignment ◽

Stage 1 ◽

Main Effects ◽

Treatment Sequences

Abstract Background Treatment of a child who has an anxiety disorder usually begins with the question of which treatment to start first, medication or psychotherapy. Both have strong empirical support, but few studies have compared their effectiveness head-to-head, and none has investigated what to do if the treatment tried first isn’t working well—whether to optimize the treatment already begun or to add the other treatment. Methods This is a single-blind Sequential Multiple Assignment Randomized Trial (SMART) of 24 weeks duration with two levels of randomization, one in each of two 12-week stages. In Stage 1, children will be randomized to fluoxetine or Coping Cat Cognitive Behavioral Therapy (CBT). In Stage 2, remitters will continue maintenance-level therapy with the single-modality treatment received in Stage 1. Non-remitters during the first 12 weeks of treatment will be randomized to either [1] optimization of their Stage 1 treatment, or [2] optimization of Stage 1 treatment and addition of the other intervention. After the 24-week trial, we will follow participants during open, naturalistic treatment to assess the durability of study treatment effects. Patients, 8–17 years of age who are diagnosed with an anxiety disorder, will be recruited and treated within 9 large clinical sites throughout greater Los Angeles. They will be predominantly underserved, ethnic minorities. The primary outcome measure will be the self-report score on the 41-item youth SCARED (Screen for Child Anxiety Related Disorders). An intent-to-treat analysis will compare youth randomized to fluoxetine first versus those randomized to CBT first (“Main Effect 1”). Then, among Stage 1 non-remitters, we will compare non-remitters randomized to optimization of their Stage 1 monotherapy versus non-remitters randomized to combination treatment (“Main Effect 2”). The interaction of these main effects will assess whether one of the 4 treatment sequences (CBT➔CBT; CBT➔med; med➔med; med➔CBT) in non-remitters is significantly better or worse than predicted from main effects alone. Discussion Findings from this SMART study will identify treatment sequences that optimize outcomes in ethnically diverse pediatric patients from underserved low- and middle-income households who have anxiety disorders. Trial registration This protocol, version 1.0, was registered in ClinicalTrials.gov on February 17, 2021 with Identifier: NCT04760275.

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Adaptive intervention for prevention of adolescent suicidal behavior after hospitalization: a pilot sequential multiple assignment randomized trial

Journal of Child Psychology and Psychiatry ◽

10.1111/jcpp.13383 ◽

2021 ◽

Author(s):

Ewa K. Czyz ◽

Cheryl A. King ◽

David Prouty ◽

Valerie J. Micol ◽

Maureen Walton ◽

...

Keyword(s):

Randomized Trial ◽

Suicidal Behavior ◽

Adaptive Intervention ◽

Multiple Assignment

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A controlled randomized trial of atypical depression: Study design and patient characteristics

Biological Psychiatry ◽

10.1016/0006-3223(94)90666-1 ◽

1994 ◽

Vol 35 (9) ◽

pp. 617

Author(s):

R.B. Jarrett ◽

M.H. Schaffer ◽

M.M. Down ◽

Q.C. Cheng ◽

C. Judd ◽

...

Keyword(s):

Randomized Trial ◽

Study Design ◽

Patient Characteristics ◽

Atypical Depression

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Evaluating Misclassification Effects on Single Sequential Treatment in Sequential Multiple Assignment Randomized Trial (SMART) Designs

Statistics in Biopharmaceutical Research ◽

10.1080/19466315.2021.1883472 ◽

2021 ◽

pp. 1-13

Author(s):

Jun He ◽

Donna K. McClish ◽

Roy T. Sabo

Keyword(s):

Randomized Trial ◽

Sequential Treatment ◽

Multiple Assignment

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Critical Decision Points for Augmenting Interpersonal Psychotherapy for Depressed Adolescents: A Pilot Sequential Multiple Assignment Randomized Trial

Journal of the American Academy of Child & Adolescent Psychiatry ◽

10.1016/j.jaac.2018.06.032 ◽

2019 ◽

Vol 58 (1) ◽

pp. 80-91 ◽

Cited By ~ 4

Author(s):

Meredith Gunlicks-Stoessel ◽

Laura Mufson ◽

Gail Bernstein ◽

Ana Westervelt ◽

Kristina Reigstad ◽

...

Keyword(s):

Randomized Trial ◽

Interpersonal Psychotherapy ◽

Decision Points ◽

Multiple Assignment

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Comparing cluster-level dynamic treatment regimens using sequential, multiple assignment, randomized trials: Regression estimation and sample size considerations

Statistical Methods in Medical Research ◽

10.1177/0962280217708654 ◽

2017 ◽

Vol 26 (4) ◽

pp. 1572-1589 ◽

Cited By ~ 13

Author(s):

Timothy NeCamp ◽

Amy Kilbourne ◽

Daniel Almirall

Keyword(s):

Randomized Trial ◽

Randomized Trials ◽

Treatment Regimens ◽

Patient Level ◽

Multiple Assignment ◽

Dynamic Treatment ◽

The Mean ◽

Cluster Randomized ◽

The Individual ◽

Cluster Level

Cluster-level dynamic treatment regimens can be used to guide sequential treatment decision-making at the cluster level in order to improve outcomes at the individual or patient-level. In a cluster-level dynamic treatment regimen, the treatment is potentially adapted and re-adapted over time based on changes in the cluster that could be impacted by prior intervention, including aggregate measures of the individuals or patients that compose it. Cluster-randomized sequential multiple assignment randomized trials can be used to answer multiple open questions preventing scientists from developing high-quality cluster-level dynamic treatment regimens. In a cluster-randomized sequential multiple assignment randomized trial, sequential randomizations occur at the cluster level and outcomes are observed at the individual level. This manuscript makes two contributions to the design and analysis of cluster-randomized sequential multiple assignment randomized trials. First, a weighted least squares regression approach is proposed for comparing the mean of a patient-level outcome between the cluster-level dynamic treatment regimens embedded in a sequential multiple assignment randomized trial. The regression approach facilitates the use of baseline covariates which is often critical in the analysis of cluster-level trials. Second, sample size calculators are derived for two common cluster-randomized sequential multiple assignment randomized trial designs for use when the primary aim is a between-dynamic treatment regimen comparison of the mean of a continuous patient-level outcome. The methods are motivated by the Adaptive Implementation of Effective Programs Trial which is, to our knowledge, the first-ever cluster-randomized sequential multiple assignment randomized trial in psychiatry.

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BestFIT Sequential Multiple Assignment Randomized Trial Results: A SMART Approach to Developing Individualized Weight Loss Treatment Sequences

Annals of Behavioral Medicine ◽

10.1093/abm/kaab061 ◽

2021 ◽

Author(s):

Nancy E Sherwood ◽

A Lauren Crain ◽

Elisabeth M Seburg ◽

Meghan L Butryn ◽

Evan M Forman ◽

...

Keyword(s):

Weight Loss ◽

Randomized Trial ◽

Controlled Trial ◽

Response Assessment ◽

Optimal Time ◽

Behavioral Weight Loss ◽

Weight Loss Treatment ◽

Adaptive Intervention ◽

Weight Losses ◽

Multiple Assignment

Abstract Background State-of-the-art behavioral weight loss treatment (SBT) can lead to clinically meaningful weight loss, but only 30–60% achieve this goal. Developing adaptive interventions that change based on individual progress could increase the number of people who benefit. Purpose Conduct a Sequential Multiple Assignment Randomized Trial (SMART) to determine the optimal time to identify SBT suboptimal responders and whether it is better to switch to portion-controlled meals (PCM) or acceptance-based treatment (ABT). Method The BestFIT trial enrolled 468 adults with obesity who started SBT and were randomized to treatment response assessment at Session 3 (Early TRA) or 7 (Late TRA). Suboptimal responders were re-randomized to PCM or ABT. Responders continued SBT. Primary outcomes were weight change at 6 and 18 months. Results PCM participants lost more weight at 6 months (−18.4 lbs, 95% CI −20.5, −16.2) than ABT participants (−15.7 lbs, 95% CI: −18.0, −13.4), but this difference was not statistically significant (−2.7 lbs, 95% CI: −5.8, 0.5, p = .09). PCM and ABT participant 18 month weight loss did not differ. Early and Late TRA participants had similar weight losses (p = .96), however, Early TRA PCM participants lost more weight than Late TRA PCM participants (p = .03). Conclusions Results suggest adaptive intervention sequences that warrant further research (e.g., identify suboptimal responders at Session 3, use PCMs as second-stage treatment). Utilizing the SMART methodology to develop an adaptive weight loss intervention that would outperform gold standard SBT in a randomized controlled trial is an important next step, but may require additional optimization work. Clinical Trial information ClinicalTrials.gov identifier; NCT02368002

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Developing the Synergy Model Patient Acuity Tool for Admission, Discharge, and Transfer

American Journal of Critical Care ◽

10.4037/ajcc2020204 ◽

2020 ◽

Vol 29 (1) ◽

pp. 61-69

Author(s):

Diane G. Byrum ◽

Eileen V. Caulfield ◽

Julia D. Burgess ◽

Tracy B. Holshouser ◽

Debra L. Daniels ◽

...

Keyword(s):

Critical Care ◽

Effect Size ◽

Standardize Patient ◽

Patient Characteristics ◽

Critical Care Nurses ◽

Level Of Care ◽

Patient Acuity ◽

Patient Response ◽

Physiological Variables ◽

Intervention Intensity

Background The Admission Discharge Transfer–Synergy Model Acuity Tool (ADT-SMAT) was developed to quantify patient intervention intensity and patient response variability and to capture nurses’ critical thinking. The tool is based on the American Association of Critical-Care Nurses Synergy Model for Patient Care. Objective To determine whether the ADT-SMAT is reliable and valid for predicting the level of care for admission, discharge, and transfer of critically ill patients. Methods Reliability was examined by using interrater reliability, intraclass coefficient, and effect size analyses to evaluate physiological variables and total calculated ADT-SMAT score in 246 patients. Content validity was determined in consultation with critical care nurses, and construct validity was examined by assessing the correlation between ADT-SMAT scores and other convergent and divergent constructs. Results The ADT-SMAT showed strong reliability for measuring the physiological variables and total score, with an intraclass coefficient of 0.930. The value of Cohen d determining the effect size for each element of the ADT-SMAT was less than 0.20 for every element, indicating that substantial differences in scoring did not occur. The validity of the ADT-SMAT requires additional testing. Conclusions This is the first study attempting to correlate Synergy Model patient characteristics and acuity while integrating nurses’ critical decision-making process. With further testing, the ADT-SMAT could be a valuable tool to quantify and standardize patient characteristics in determining the appropriate level of care associated with admission, discharge, and transfer decisions.

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